| Hypoestrogenism | |
|---|---|
| Other names | Estrogen deficiency |
| Specialty | Gynecology |
Hypoestrogenism, orestrogen deficiency, refers to a lower than normal level ofestrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk ofcardiovascular disease,[1] and has been linked to diseases likeurinary tract infections[2] andosteoporosis.
In women, low levels of estrogen may cause symptoms such ashot flashes,sleeping disturbances, decreasedbone health,[3] and changes in thegenitourinary system. Hypoestrogenism is most commonly found in women who arepostmenopausal, haveprimary ovarian insufficiency (POI), or are presenting withamenorrhea (absence ofmenstrual periods). Hypoestrogenism includes primarily genitourinary effects, including thinning of thevaginal tissue layers and an increase invaginal pH. With normal levels of estrogen, the environment of the vagina is protected againstinflammation,infections, andsexually transmitted infections.[4] Hypoestrogenism can also occur in men, for instance due tohypogonadism.
There are bothhormonal and non-hormonal treatments to prevent the negative effects of low estrogen levels and improve quality of life.
Presentations of low estrogen levels include hot flashes, which are sudden, intense feelings of heat predominantly in the upper body, causing the skin to redden as if blushing. They are believed to occur due to the narrowing of the thermonuclear zone in thehypothalamus, making the body more sensitive to body temperature changes.[5] Night disturbances are also common symptoms associated with hypoestrogenism. People may experience difficulty falling asleep, waking up several times a night, and early awakening with different variability between races and ethnic groups.[6]
Other classic symptoms include both physical and chemical changes of thevulva, vagina, andlower urinary tract.[7] Genitals go throughatrophic changes such as losing elasticity, losing vaginalrugae, and increasing of vaginal pH,[8] which can lead to changes in thevaginal flora and increase the risk of tissue fragility andfissure. Other genital signs include dryness or lack oflubrication, burning, irritation, discomfort or pain, as well as impaired function.[9] Low levels of estrogen can lead to limitedgenital arousal and causedyspareunia, or painful sexual intercourse because of changes in the four layers of the vaginal wall.[10] People with low estrogen will also experience higher urgency to urinate anddysuria, or painful urination.[failed verification] Hypoestrogenism is also considered one of the major risk factors for developing uncomplicated urinary tract infection in postmenopausal women who do not takehormone replacement therapy.[11]
Estrogen contributes to bone health in several ways;[12] low estrogen levels increasebone resorption viaosteoclasts andosteocytes, cells that help withbone remodeling,[13] making bones more likely to deteriorate and increase risk of fracture. The decline in estrogen levels can ultimately lead to more serious illnesses, such asscoliosis[14] or type Iosteoporosis, a disease that thins and weakens bones, resulting in lowbone density and fractures.[15][16] Estrogen deficiency plays an important role in osteoporosis development for both genders, and it is more pronounced for women and at younger (menopausal) ages by five to ten years compared with men. Females are also at higher risk forosteopenia andosteoporosis.[16]
A variety of conditions can lead to hypoestrogenism:menopause is the most common.[5] Primary ovarian insufficiency (premature menopause) due to varying causes, such asradiation therapy,chemotherapy, or a spontaneous manifestation, can also lead to low estrogen andinfertility.[17]
Hypogonadism (a condition where thegonads –testes for men andovaries for women – have diminished activity) can decrease estrogen.[18] Inprimary hypogonadism, elevated serumgonadotropins are detected on at least two occasions several weeks apart, indicating gonadal failure.[18] Insecondary hypogonadism (where the cause ishypothalamic orpituitary dysfunction) serum levels of gonadotropins may be low.[19]
Other causes include certain medications,gonadotropin insensitivity,inborn errors of steroid metabolism (for example,aromatase deficiency,17α-hydroxylase deficiency,17,20-lyase deficiency,3β-hydroxysteroid dehydrogenase deficiency, andcholesterol side-chain cleavage enzyme or steroidogenic acute regulatory protein deficiency) and functional amenorrhea.[medical citation needed]
Lowendogenous estrogen levels can elevate the risk ofcardiovascular disease in women who reachearly menopause.[1] Estrogen is needed to relax arteries using endothelial-derivednitric oxide resulting in betterheart health by decreasing adverseatherogenic effects.[20] Women with POI may have an increased risk of cardiovascular disease due to low estrogen production.[21]
Estrogen deficiency has both vaginal and urologic effects; the female genitalia and lower urinary tract share commonestrogen receptor function due to their embryological development. Estrogen is avasoactive hormone (one that affects blood pressure) which stimulates blood flow and increases vaginal secretions and lubrication. Activated estrogen receptors also stimulate tissue proliferation in the vaginal walls, which contribute to the formation ofrugae. This rugae aids in sexual stimulation by becoming lubricated, distended, and expanded.[22]
Genitourinary effects of low estrogen include thinning of the vaginalepithelium, loss of vaginal barrier function,[clarification needed] decrease of vaginal folding, decrease of the elasticity of the tissues, and decrease of the secretory activity of theBartholin glands, which leads to traumatization of the vaginal mucosa and painful sensations. This thinning of the vaginal epithelium layers can increase the risk of developing inflammation and infection, such as urinary tract infection.[4]
The vagina is largely dominated by bacteria from the genusLactobacillus, which typically comprise more than 70% of the vaginal bacteria in women. These lactobacilli processglycogen and its breakdown products, which result in a maintained low vaginal pH. Estrogen levels are closely linked to lactobacilli abundance and vaginal pH, as higher levels of estrogen promote thickening of the vaginal epithelium and intracellular production of glycogen. This large presence of lactobacilli and subsequent low pH levels are hypothesized to benefit women by protecting againstsexually transmitted pathogens and opportunistic infections, and therefore reducing disease risk.[23]
Hypoestrogenism is typically found in menopause and aids in diagnosis of other conditions such as POI and functional amenorrhea.[17][24] Estrogen levels can be tested through several laboratory tests: vaginal maturation index,[clarification needed]progestogen challenge test, and vaginal swabs for smallparabasal cells.[19]
Menopause is usually diagnosed through symptoms of vaginal atrophy, pelvic exams, and taking a comprehensive medical history consisting of last menstruation cycle. There is no definitive testing available for determining menopause as the symptom complex is the primary indicator[5] and because the lower levels of estradiol are harder to accurately detect after menopause.[25] However, there can be laboratory tests done to differentiate between menopause and other diagnoses.[citation needed]
Functional hypothalamic amenorrhea (FHA) is diagnosed based on findings of amenorrhea lasting three months or more, low serum hormone of gonadotropins and estradiol.[26] Since common causes of FHA include exercising too much, eating too little, or being under too much stress, diagnosis of FHA includes assessing for any changes in exercise, weight, and stress. In addition, evaluation of amenorrhea includes a history and physical examination, biochemical testing, imaging, and measuring estrogen level. Examination of menstrual problems and clinical tests to measure hormones such as serumprolactin,thyroid-stimulating hormone, andfollicle-stimulating hormone (FSH) can help rule out other potential causes of amenorrhea. These potential conditions includehyperprolactinemia, POI, andpolycystic ovary syndrome.[27]
Primary ovarian insufficiency, also known as premature ovarian failure, can develop in women before the age of forty as a consequence of hypergonadotropic hypogonadism.[19] POI can present as amenorrhea and has similar symptoms to menopause, but measuring FSH levels is used for diagnosis.[21]
Hormone replacement therapy (HRT) can be used to treat hypoestrogenism and menopause related symptoms, and low estrogen levels in bothpremenopausal and postmenopausal women. Low-dose estrogen medications are approved by the U.S.Food and Drug Administration for treatment of menopause-related symptoms. HRT can be used with or without aprogestogen to improve symptoms such as hot flashes, sweating, trouble sleeping, vaginal dryness and discomfort.[28] The FDA recommends HRT to be avoided in women with a history or risk of breast cancer, undiagnosed genital bleeding, untreated high blood pressure, unexplained blood clots, or liver disease.[28]
HRT for the vasomotor symptoms of hypoestrogenism include different forms of estrogen, such as conjugated equine estrogens, 17β-estradiol, transdermal estradiol, ethinyl estradiol, and the estradiol ring.[28] In addition to HRT, there are common progestogens that are used to protect the inner layer of the uterus, the endometrium. These medications includemedroxyprogesterone acetate,progesterone,norethisterone acetate, anddrospirenone.[28]
Non-pharmacological treatment of hot flashes includes using portable fans to lower the room temperature, wearing layered clothing, and avoiding tobacco, spicy food, alcohol and caffeine. There is a lack of evidence to support other treatments such asacupuncture, yoga, and exercise to reduce symptoms.[29]
Estrogens are also important in male physiology.[30][31][32] Hypoestrogenism can occur in men due tohypogonadism.[33] Very rare causes includearomatase deficiency andestrogen insensitivity syndrome.[30][31][32] Medications can also be a cause of hypoestrogenism in men.[34][35] Hypoestrogenism in men can lead toosteoporosis, among other symptoms.[30][31][32] Estrogens may also be positively involved insexual desire in men.[33][36]